Current Drug Target -CNS & Neurological Disorders

Stephen D. Skaper
Department of Pharmaceutical and Pharmacological Sciences
University of Padova


Ionotropic Glutamate Receptors as Therapeutic Targets in Schizophrenia

Author(s): Joseph T. Coyle, Guochuan Tsai and Donald C. Goff

Affiliation: 115 Mill Street, Belmont, MA 02478, USA

Keywords: d-serine, glycine, nmda, schizophrenia, glutamate receptors, dissociative anaesthetics


Evidence implicating dysfunction of glutamatergic neurotransmission rests largely on the finding that antagonists of the NMDA subtype of glutamate receptor, especially the dissociative anesthetics like ketamine, can reproduce the full range of symptoms as well as the physiologic manifestation of schizophrenia such as hypofrontality, impaired prepulse inhibition and enhanced subcortical dopamine release. To test the hypothesis that schizophrenia may result from NMDA receptor hypofunction a number of clinical trials have examined the effects of agents that act on the glycine modulatory site on the NMDA receptor. Glycine, D-serine, and the partial agonist, D-cycloserine, have been shown to improve cognition and decrease negative symp- toms in schizophrenic subjects receiving typical antipsychotics. Results with D-cycloserine suggest that clozapine may enhance glycine modulatory site occupancy. Preliminary results with an allosteric modulator of the AMPA subtype of glutamate receptor suggest enhanced cognitive functions in subjects treated with clozapine.

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Article Details

Page: [183 - 189]
Pages: 7
DOI: 10.2174/1568007024606212